Dissecting complex disease has become more feasible due to the availability of large-scale DNA resources and advances in high-throughput genomic technology. While these tools help scientists identify potential susceptibility loci, subjects with very specific relevant genotypes are needed for clinical phenotyping and toxicity studies. For this reason, NIEHS has developed the Environmental Polymorphism Registry (EPR);a resource of subjects and their DNAs to use for translational research of environmental diseases. Over 15,000 individuals of diverse sex, age, race and ethnicity have been recruited by the EPR. DNA was isolated from their bloods and coded with personal identification numbers (PINs) linked back to their identities. This linked resource of subjects and their DNAs allow scientists to screen for individuals with genotypes of interest and invite them to participate in follow-up studies. The EPR further aims to characterize health effects of polymorphisms, and to conduct epidemiologic studies of gene-environment interactions. The Molecular Genetics Core Facility (MGCF) infrastructure was created to perform nucleic acid sample isolation, sample management and genetics studies to support the EPR and other genetics efforts at NIEHS, and currenty manages extraction, sample databasing and genotyping for the EPR. This month the MGCF will complete an Illumina genotyping study of 768 SNPs across 4000 EPR samples. During the past year, robotic automation in the MGCF was improved to further decrease the cost of genetic studies performed at NIEHS. We have continued to develop a dynamic web portal to manage the core facility, and an associated database to track both work product and cost of each study. Cost-accounting features were improved this year to make annual and quarterly reporting automated. We established automated gene resequencing infrastructure at 1/64 scale, which provides support from primer design through data analysis, while dramatically reducing cost per reaction. We also developed an automated gel-free mouse tail genotyping method to reduce labor and expense of this time consuming and costly aspect of maintaining mouse colonies. Both the methods automation and methods development aspects of our workgroup offer opportunities for accelerated development of new therapies for prevention of environmentally induced disease.